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Provided are polymeric nitrones comprising polymerized units of (a)
acrylates of Formula I:
##STR00001##
wherein R.sup.1 and R.sup.2 are as defined herein; and (b)
nitrone-pendant esters of Formula II:
##STR00002##
wherein R.sup.3 and R.sup.4 are as defined herein, and Z is a nitrone
substituent of Formula III:
##STR00003##
wherein R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11,
R.sup.12, R.sup.13, and R.sup.14 are as defined herein, and wherein the
sum of m+n is a number from 10 to 50, and the ratio of m to n is from 1:1
to 20:1.

1. A polymeric nitrone comprising polymerized units of: (a) acrylates of
Formula I: ##STR00025## wherein R.sup.1 is H or CH.sub.3; and R.sup.2
is C.sub.1-C.sub.6 alkyl, phenyl, hydroxy C.sub.1-C.sub.6 alkyl,
dihydroxy C.sub.1-C.sub.6 alkyl, polyoxyalkylene, N,N-dimethylamino
C.sub.2-C.sub.6 alkyl, N,N-diethylamino C.sub.2-C.sub.4 alkyl; and (b)
nitrone-pendant esters of Formula II: ##STR00026## wherein R.sup.3 is H
or --COOH; R.sup.4 is H or CH.sub.3, and Z is a nitrone substituent of
Formula III: ##STR00027## wherein R.sup.5, R.sup.6, R.sup.7, R.sup.8,
and R.sup.9 are independently H, --OH, C.sub.1-C.sub.6 alkoxy, --COOH,
--COO.sup.-M.sup.+ or --O.sup.-M.sup.+, where M.sup.+ is a sodium,
potassium, or ammonium ion; and R.sup.10, R.sup.11, R.sup.12, R.sup.13,
and R.sup.14 are independently H, --OH, C.sub.1-C.sub.6 alkoxy, --COOH,
--COO.sup.-M.sup.+ or --O.sup.-M.sup.+, where M.sup.+ is a sodium,
potassium, or ammonium ion, or a substituent of Formula IV: ##STR00028##
wherein R.sup.15, R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are
independently H, --OH, C.sub.1-C.sub.6 alkoxy, --COOH, --COO.sup.-M.sup.+
or --O.sup.-M.sup.+, where M.sup.+ is a sodium, potassium, or ammonium
ion, wherein the ester of Formula II is attached to the nitrone of
Formula III at either of the phenyl rings thereon, with the proviso that
if R.sup.10, R.sup.11, R.sup.12, R.sup.13, or R.sup.14 is a substituent
of Formula IV, then the ester of Formula II is attached to the nitrone of
Formula III at the phenyl ring opposite the ring on which the substituent
of Formula IV is attached, and the proviso that not more than one of
R.sup.10, R.sup.11, R.sup.12, R.sup.13, or R.sup.14 can be a substituent
of Formula IV, and the further proviso that at least two of R.sup.5,
R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12,
R.sup.13, R.sup.14, R.sup.15, R.sup.16, R.sup.17, R.sup.18 and R.sup.19
are --OH; and wherein the sum of m+n is a number from 10 to 50, and the
ratio of m to n is from 1:1 to 20:1.

4. The polymeric nitrone of claim 1 wherein one of R.sup.10, R.sup.11,
R.sup.12, R.sup.13, and R.sup.14 is a substituent of Formula IV, and the
ester of Formula II is attached to the nitrone of Formula III at the
phenyl ring opposite the ring on which the substituent of Formula IV is
attached.

5. The polymeric nitrone of claim 4 wherein the acrylate of Formula I is:
##STR00029## and the nitrone-pendant ester of Formula II is:
##STR00030##

6. The polymeric nitrone of claim 4 wherein: the acrylate of Formula I
is: ##STR00031## and the nitrone-pendant ester of Formula II is:
##STR00032##

7. A personal care composition comprising: (1) a polymeric nitrone
comprising polymerized units of: (a) acrylates of Formula I:
##STR00033## wherein R.sup.1 is H or CH.sub.3; and R.sup.2 is
C.sub.1-C.sub.6 alkyl, phenyl, hydroxy C.sub.1-C.sub.6 alkyl, dihydroxy
C.sub.1-C.sub.6 alkyl, polyoxyalkylene, N,N-dimethylamino C.sub.2-C.sub.6
alkyl, N,N-diethylamino C.sub.2-C.sub.4 alkyl; and (b) nitrone-pendant
esters of Formula II: ##STR00034## wherein R.sup.3 is H or --COOH;
R.sup.4 is H or CH.sub.3, and Z is a nitrone substituent of Formula III:
##STR00035## wherein R.sup.5, R.sup.6, R.sup.7, R.sup.8, and R.sup.9
are independently H, --OH, C.sub.1-C.sub.6 alkoxy, --COOH,
--COO.sup.-M.sup.+ or --O.sup.-M.sup.+, where M.sup.+ is a sodium,
potassium, or ammonium ion; and R.sup.10, R.sup.11, R.sup.12, R.sup.13,
and R.sup.14 are independently H, --OH, C.sub.1-C.sub.6 alkoxy, --COOH,
--COO.sup.-M.sup.+ or --O.sup.-M.sup.+, where M.sup.+ is a sodium,
potassium, or ammonium ion, or a substituent of Formula IV: ##STR00036##
wherein R.sup.15, R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are
independently H, --OH, C.sub.1-C.sub.6 alkoxy, --COOH, --COO.sup.-M.sup.+
or --O.sup.-M.sup.+, where M.sup.+ is a sodium, potassium, or ammonium
ion, wherein the ester of Formula II is attached to the nitrone of
Formula III at either of the phenyl rings thereon, with the proviso that
if R.sup.10, R.sup.11, R.sup.12, R.sup.13, or R.sup.14 is a substituent
of Formula IV, then the ester of Formula II is attached to the nitrone of
Formula III at the phenyl ring opposite the ring on which the substituent
of Formula IV is attached, and the proviso that not more than one of
R.sup.10, R.sup.11, R.sup.12, R.sup.13, or R.sup.14 can be a substituent
of Formula IV, and the further proviso that at least two of R.sup.5,
R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12,
R.sup.13, R.sup.14, R.sup.15, R.sup.16, R.sup.17, R.sup.18, and R.sup.19
are --OH; and wherein the sum of m+n is a number from 10 to 50, and the
ratio of m to n is from 1:1 to 20:1; and (2) a dermatologically
acceptable carrier.

10. The personal care composition of claim 7 wherein one of R.sup.10,
R.sup.11, R.sup.12, R.sup.13, or R.sup.14 is a substituent of Formula IV,
and the ester of Formula II is attached to the nitrone of Formula III at
the phenyl ring opposite the ring on which the substituent of Formula IV
is attached.

11. The personal care composition of claim 10 wherein the acrylate of
Formula I is: ##STR00037## and the nitrone-pendant ester of Formula II
is: ##STR00038##

12. The personal care composition of claim 10 wherein the acrylate of
Formula I is: ##STR00039## and the nitrone-pendant ester of Formula II
is: ##STR00040##

13. A cosmetic method of treating skin comprising applying to the skin
the composition of claim 8.

14. A method for inhibiting the degradation of collagen in skin, the
method comprising: topically administering to the skin an effective
amount of the composition of claim 7.

15. A method for reducing the visible signs of aging, the method
comprising: applying to skin in need of such treatment the composition of
claim 7.

Description

FIELD OF THE INVENTION

[0001] This invention relates generally to compounds and compositions that
are useful as antioxidants in personal care formulations. The compounds
are polymeric nitrones that contain both nitrone and phenolic
functionalities.

BACKGROUND

[0002] Personal care compositions are important products for most
consumers. Personal care compositions contain a variety of additives that
provide a wide array of benefits to the composition.

[0003] Antioxidants are among the additives commonly used in personal care
compositions. Antioxidants help protect the skin from the damaging
effects of free radicals caused by various environmental stresses, such
as exposure to UV rays. Free radicals include, for example, singlet
oxygen. Free radicals cause damage to the skin with the end result being
a loss of elasticity of the skin and the appearance of wrinkles leading
to premature aging of the skin.

[0004] Based on the physiological mechanism of the aging process,
oxidative stress due to increased level of reactive oxygen species (ROS)
especially caused by physiological stress or solar ultraviolet radiation
can accelerate skin aging. There is evidence that intrinsic and extrinsic
aging (i.e., photoaging) have several overlapping biochemical and
molecular mechanisms. Type I collagen constitutes the major structural
component of dermal connective tissue and provides dermis with tensile
strength and stability. Degradation of collagen in the dermis has been
reported in intrinsic aged and photoaged skin. Additionally, a major
signaling pathway contributing to photoaging by ROS is the up-regulation
of matrix metalloproteinase-1 (MMP-1), which leads to degradation of
dermal collagen, associated with aging spots and wrinkles. Therefore,
stronger antioxidants are needed as potential anti-aging ingredients to
provide protection.

[0005] One such antioxidant that has been studied, as disclosed in WO
2012/150370, is resveratrol (3,5,4'-trihydroxy-trans-stilbene).
Resveratrol is a naturally occurring polyphenolic compound found in the
skin of grapes and other fruits. It has been investigated in the context
of its potential chemopreventive properties against skin damage from UV
exposure and against ROS induced damage associated with brain function,
heart disease, and cancer. However, the natural abundance of resveratrol
is low, and it is thus very expensive.

[0006] Consequently, there is a need to develop new antioxidant
compositions for use in personal care, including compositions that
mitigate degradation of collagen in skin.

STATEMENT OF INVENTION

[0007] We have now found that polymeric polyhydroxy nitrones have
equivalent efficacy as radical scavengers at lower concentrations (as
measured by duration of antioxidant protection), or higher efficacy (less
oxidative damage and/or longer antioxidant protection) at equivalent
concentrations as compared to conventional antioxidants. It has also been
found that the performance of nitrones cannot be achieved by simply
adding two different antioxidants, e.g., one with a phenolic
functionality and another with nitrone functionality. Rather, the
presence of both functionalities in the same molecule is an important
aspect of their favorable performance.

[0017] R.sup.10, R.sup.11, R.sup.12, R.sup.13, and R.sup.14 are
independently H, --OH, C.sub.1-C.sub.6 alkoxy, --COOH, --COO.sup.-M.sup.+
or --O.sup.-M.sup.+, where M.sup.+ is a sodium, potassium, or ammonium
ion, or a substituent of Formula IV:

##STR00007##

wherein

[0018] R.sup.15, R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are
independently H, --OH, C.sub.1-C.sub.6 alkoxy, --COOH, --COO.sup.-M.sup.+
or --O.sup.-M.sup.+, where M.sup.+ is a sodium, potassium, or ammonium
ion; [0019] wherein the ester of Formula II is attached to the nitrone of
Formula III at either of the phenyl rings thereon, with the proviso that
if R.sup.10, R.sup.11, R.sup.12, R.sup.13, or R.sup.14 is a substituent
of Formula IV, then the ester of Formula II is attached to the nitrone of
Formula III at the phenyl ring opposite the ring on which the substituent
of Formula IV is attached, and the proviso that not more than one of
R.sup.10, R.sup.11, R.sup.12, R.sup.13, or R.sup.14 can be a substituent
of Formula IV, and the further proviso that at least two of R.sup.5,
R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12,
R.sup.13, R.sup.14 R.sup.15, R.sup.16, R.sup.17, R.sup.18, and R.sup.19
are --OH, and wherein the sum of m+n is a number from 10 to 50, and the
ratio of m to n is from 1:1 to 20:1.

[0020] Another aspect of the invention provides a personal care
composition comprising (a) the antioxidant polymeric nitrone described
above, and (b) a dermatologically acceptable carrier.

[0021] In another aspect, the invention provides a cosmetic method of
treating skin which comprises applying to the skin a polymeric nitrone
composition as described herein.

[0022] In a still further aspect, there is provided a method for
inhibiting the degradation of collagen, the method comprising topically
administering to skin an effective amount of an antioxidant polymeric
nitrone composition as described herein.

[0023] In a yet further aspect, there is provided a method for reducing
the visible signs of aging, the method comprising applying to skin in
need of such treatment an antioxidant polymeric nitrone composition as
described herein.

DETAILED DESCRIPTION

[0024] Unless otherwise indicated, numeric ranges, for instance as in
"from 2 to 10," are inclusive of the numbers defining the range (e.g., 2
and 10). Unless otherwise indicated, ratios, percentages, parts, and the
like are by weight. "Room temperature," as used in this specification, is
the ambient temperature, for example, 20-25.degree. C.

[0025] "Alkyl," as used in this specification, encompasses straight and
branched chain aliphatic hydrocarbon groups having the indicated number
of carbon atoms. If no number is indicated, then 1-6 alkyl carbons are
contemplated. Unless otherwise indicated, the alkyl group is optionally
substituted with 1, 2, or 3, preferably 1 or 2, more preferably 1,
substituents that are compatible with the syntheses described herein.
Such substituents include, but are not limited to, nitro, halogen,
carboxylic acids (e.g., C.sub.0-C.sub.6--COOH), C.sub.2-C.sub.6 alkene,
cyano, amido, and/or ester. Unless otherwise indicated, the foregoing
substituent groups are not themselves further substituted.

[0026] As noted above, in one aspect the invention provides an antioxidant
polymeric nitrone composition comprising polymerized units of (a)
acrylates of Formula I and (b) nitrone-pendant esters of Formula II,
wherein the sum of m+n is a number from 10 to 50, and the ratio of m to n
is from 1:1 to 20:1. In certain preferred embodiments, the sum of m+n is
a number from 10 to 35, and more preferably from 15 to 25. In certain
preferred embodiments, the ratio of m to n is from 5:1 to 10:1. In
certain embodiments, the polymer contains sufficient acrylate polymers to
be partially water soluble. As used herein the term "partially water
soluble" means that at least 0.5 weight percent of the polymeric nitrone
is soluble in water at room temperature based on the total weight of the
composition.

[0028] In certain embodiments R.sup.10, R.sup.11, R.sup.12, R.sup.13, and
R.sup.14 are independently H, --OH, C.sub.1-C.sub.6 alkoxy, --COOH,
--COO.sup.-M.sup.+ or --O.sup.-M.sup.+, where M.sup.+ is a sodium,
potassium, or ammonium ion. In certain of such embodiments, the nitrone
of Formula III comprises one of those specified in Table 1:

[0029] In certain embodiments one of R.sup.10, R.sup.11, R.sup.12,
R.sup.13, and R.sup.14 is a substituent of Formula IV, and the ester of
Formula II is attached to the nitrone of Formula III at the phenyl ring
opposite the ring on which the substituent of Formula IV is attached. In
certain of such embodiments, the nitrone of Formula III comprises one of
those specified in Table 2:

[0030] In certain preferred embodiments, the acrylate of Formula I is:

##STR00018##

and the nitrone-pendant ester of Formula II is:

##STR00019##

[0031] In certain preferred embodiments, the acrylate of Formula I is:

##STR00020##

and the nitrone-pendant ester of Formula II is:

##STR00021##

[0032] The nitrone substituents of Formula III may be readily prepared by
those skilled in the art using known synthetic techniques. Certain
embodiments in which none of R.sup.10, R.sup.11, R.sup.12, R.sup.13, and
R.sup.14 is a substituent of Formula IV may be prepared, for example, by
the reaction of a phenyl aldehyde compound (containing one or more
hydroxyl groups on the phenyl, such as 4-hydroxybenzaldehyde) with a
benzylhydroxylamine compound (also containing one or more hydroxyl groups
on the phenyl, such as 3,4-dihydroxybenzylhydroxylamine), followed by
isolation and purification of the desired product. Certain embodiments in
which one of R.sup.10, R.sup.11, R.sup.12, R.sup.13, and R.sup.14 is a
substituent of Formula IV may be prepared, for example, by the reaction
of a stilbene aldehyde compound (possibly containing one or more hydroxyl
groups, such as (E)-2-hydroxy-5-(4-hydroxy-3-methoxystyryl)benzaldehyde)
with a benzylhydroxylamine compound (also possibly containing one or more
hydroxyl groups on the phenyl, such as 3,4-dihydroxybenzylhydroxylamine),
followed by isolation and purification of the desired product.

[0033] The polymeric nitrones of the present invention may be readily
prepared by those skilled in the art using known synthetic techniques,
for example, by bulk polymerization or emulsion polymerization. Certain
embodiments in which R.sup.3 and R.sup.4 of the nitrone-pendant ester of
Formula II are --COOH and H, respectively, can be prepared, for example,
by copolymerizing an acrylate of Formula I, e.g., methyl acrylate, and
maleic anhydride in ethyl acetate using 2,2'-azobisisobutyronitrile as an
initiator, replacing the ethyl acetate with 1,4-dioxane, and reacting the
copolymer solution with a nitrone of Formula III. Certain embodiments in
which R.sup.3 and R.sup.4 of the nitrone-pendant ester of Formula II are
both H, and the acrylate of Formula I is, for example, diethyleneglycol
methyl ether acrylate, can be prepared, for example, by solution
polymerization of acryloyl chloride in tetrahydrofuran using
2,2'-azobisisobutyronitrile as an initiator to obtain polyacryloyl
chloride, replacing the tetrohydrofuran with 1,4-dioxane, and reacting
sequentially first with diethylene glycol methyl ether and triethylamine,
and then with a nitrone of Formula III and triethylamine

[0034] In another aspect, the invention provides a personal care
composition comprising (a) the antioxidant polymer nitrone compositions
described herein and (b) a dermatologically acceptable carrier. A person
of ordinary skill in the art can readily determine the effective amount
of the inventive antioxidant polymeric nitrone that should be used in a
particular composition in order to provide the benefits described herein
(e.g., free radical scavenging and inhibition of collagen degradation),
via a combination of general knowledge of the applicable field as well as
routine experimentation where needed. By way of non-limiting example, the
amount of the polymeric nitrone in the composition of the invention may
be in the range of from 0.01 to 5 weight percent, preferably from 0.05 to
3 weight percent, and more preferably from 0.1 to 1 weight percent, based
on the total weight of the composition.

[0035] Compositions of the invention also include a dermatologically
acceptable carrier. Such material is typically characterized as a carrier
or a diluent that does not cause significant irritation to the skin and
does not negate the activity and properties of active agent(s) in the
composition. Examples of dermatologically acceptable carriers that are
useful in the invention include, without limitation, emulsions, creams,
aqueous solutions, oils, ointments, pastes, gels, lotions, milks, foams,
suspensions, powders, or mixtures thereof. In some embodiments, the
composition contains from about 99.99 to about 50 percent by weight of
the dermatologically acceptable carrier, based on the total weight of the
composition.

[0036] The dermatologically acceptable carrier of the invention may also
include, for instance, water, a thickener, an emollient, an emulsifier, a
humectant, a surfactant, a suspending agent, a film forming agent, a foam
building agent, a preservative, an antifoaming agent, UV filters, a
fragrance, a lower monoalcoholic polyol, a high boiling point solvent, a
propellant, a colorant, a pigment, glycerin, a mineral oil, silicone feel
modifiers, triglycerides, polyolefins, waxes, preservatives, emollients,
or mixtures thereof.

[0038] The composition of the invention may be, for example, in the form
of an oil, a gel, a solid stick, a lotion, a cream, a milk, an aerosol, a
spray, a foam, a mousse, an ointment or a fatty ointment or a powder.

[0039] Compositions of the invention may be used in a variety of personal
care applications, such as in cosmetics and in skin care (e.g., lotions,
creams, oils, topical medicines, and sunscreens).

[0040] The compositions of the invention may be manufactured by processes
well known in the art, e.g., by means of conventional mixing, dissolving,
granulating, emulsifying, encapsulating, entrapping or lyophilizing
processes.

[0041] As noted above, compositions of the invention, containing a
compound of Formula I, are highly effective as radical scavengers. They
exhibit significantly better antioxidant attributes compared to
previously known antioxidants for personal care applications. Furthermore
it has been found that the performance of nitrones that have phenolic
groups cannot be achieved by simply adding two different antioxidants,
one with a phenolic functionality and another with nitrone functionality.
Rather, the presence of both functionalities in the same molecule is an
important aspect of their favorable performance.

[0042] The cosmetic compositions of the invention are useful for the
treatment and protection of skin from free radicals caused, for instance,
by exposure to ultraviolet light, such as UVA and UVB rays, as well as
other harmful forms of radiation, such as long wave infrared .

[0043] Thus, for instance, the cosmetic compositions may be used in a
method for inhibiting the degradation of collagen. According to such
method, an effective amount of the composition may be topically
administering to skin in need of such treatment.

[0044] The compositions may also be used in a method for reducing the
visible signs of aging, which may result from the radical induced
degradation of collagen in the skin, by applying to skin in need of such
treatment the composition. Visible signs of aging may include, for
instance, development of textural discontinuities such as wrinkles and
coarse deep wrinkles, skin lines, crevices, bumps, large pores, or
unevenness or roughness, reducing fine lines, loss of skin elasticity
(loss and/or inactivation of functional skin elastin), sagging (including
puffiness in the eye area and jowls), loss of skin firmness, loss of skin
tightness, loss of skin recoil from deformation, discoloration (including
undereye circles), blotching, sallowness, hyperpigmented skin regions
such as age spots and freckles, keratoses, abnormal differentiation,
hyperkeratinization, elastosis, and other histological changes in the
stratum corneum, dermis, epidermis, the skin vascular system (e.g.,
telangiectasia or spider vessels), and underlying tissues, especially
those proximate to the skin.

[0045] In practicing the methods of the invention, the cosmetic
composition are generally administered topically by applying or spreading
the compositions onto the skin. A person of ordinary skill in the art can
readily determine the frequency with which the cosmetic compositions
should be applied. The frequency may depend, for example, on the amount
of sunlight that an individual is likely to encounter in a given day
and/or the sensitivity of the individual to sunlight. By way of
non-limiting example, administration on a frequency of at least once per
day may be desirable.

[0046] Some embodiments of the invention will now be described in detail
in the following Examples.

[0047] A 100 mL 1-neck flask was equipped with a stir bar and a 3-way
stopcock. Methyl acrylate (MA, 9.56 grams, 0.111 moles) and maleic
anhydride (MAnh, 3.3 grams, 0.0337 moles) were dissolved in the flask in
50 mL of ethyl acetate. The flask was purged with nitrogen, sealed, and
cooled in a dry ice/isopropanol bath. After freezing, the flask was
placed under vacuum, re-sealed, and then allowed to warm to room
temperature. This process was repeated 4 additional times. The purged
monomer solution was combined with 0.46 grams of
2,2'-azobis(2-methylpropionitrile) (AIBN). The flask was again sealed,
and then heated to 50.degree. C. for 18 hours. Gel permeation
chromatography showed the presence of a trace of MAnh to be present. The
polymer solution volume obtained was 63.8 mL, which had a MA content of
0.111 moles (1.74 mmoles/mL) and a MAnh content of 0.0337 moles (0.528
mmoles/ML).

[0048] A 1.3 mL aliquot of polymer substrate PMA-c-MAnh as prepared above
was transferred to a small vial. This aliquot contained 0.528 mmoles of
MAnh. The ethyl acetate was removed under a stream of dry nitrogen. The
residue was combined with 5.0 mL of dry 1,4-dioxane and a solution of
0.1369 grams (0.528 mmoles) of the nitrone
dihydroxyphenyl)-N-(2-hydroxybenzylidene)methanamine oxide (SAL-34DHBzHA)
dissolved in an additional 10 mL of 1,4-dioxane. The vial was sealed and
placed into an oven maintained at 75.degree. C. After 24 hours, the vial
was removed from the oven, and was allowed to cool to room temperature.
Gel permeation chromatography analysis of the reaction mixture indicated
that there was no free nitrone remaining. The solvent was removed from
the reaction mixture by rotary evaporation to give 0.767 grams of product
as a dark red oil. .sup.1H-NMR analysis indicated that the ratio of
maleic acid to nitrone was about 5 to 1 based on the ratio of methyl
ester to aryl hydrogens.

[0049] Freshly distilled acryloyl chloride (AC, 11.4 grams, 0.126 moles)
was mixed with 25 mL of inhibitor-free anhydrous tetrahydrofuran (THF) in
a flask. The flask was purged with nitrogen, sealed, and cooled in a dry
ice/isopropanol bath. After freezing, the flask was placed under vacuum,
re-sealed, and then allowed to warm to room temperature. This process was
repeated 4 additional times. The purged monomer solution was combined
with 0.48 grams of 2,2'-azobis(2-methylpropionitrile) (AIBN), and the
mixture was heated at 50.degree. C. overnight to result in a solution
containing 3.5M polyacryloyl chloride (PAC) in THF (3.5 mmoles/mL).

[0050] The polyacryloyl chloride--diethyleneglycol methyl ether acrylate
copolymer was prepared according to the procedure described in W. Zou, et
al., Polymer International, 60(5), 751 (2011). A 1.0 mL aliquot of the
above PAC solution in THF was transferred to a small vial, and the THF
was removed under a stream of dry nitrogen. Dry 1,4-dioxane (5.0 mL) was
then added to the solution, followed by 0.245 grams (2.04 mmoles) of
diethylene glycol methyl ether. The vial was sealed and placed into an
oven maintained at 75.degree. C. After 24 hours, the vial was removed
from the oven, and was allowed to cool to room temperature. The
PAC-c-DEGMEA solution contained about 2.04 mmoles of diethyleneglycol
methyl ether acrylate and 1.46 mmoles about 1.46 mmoles of acryloyl
chloride.

[0051] A 1.0 mL aliquot of polymer substrate PAC-c-DEGMEA as prepared
above was transferred to a small vial. This aliquot contained 1.46 mmoles
of acryloyl chloride. The THF was removed under a stream of dry nitrogen.
The residue was combined with 5.0 mL of 1,4-dioxane and a solution of
0.413 grams (1.46 mmoles) of nitrone
dihydroxyphenyl)-N-(2,4-dihydroxybenzylidene)methanamine oxide
(24DHBz-24DHBzHA) dissolved in an additional 10 mL of 1,4-dioxane. The
vial was sealed and placed into an oven maintained at 75.degree. C. The
reaction mixture was checked after a short time at 75.degree. C., and it
was found that not all of the nitrone had dissolved. DMSO (1.5 mL) was
added to the mixture, and a clear solution resulted. The vial was
returned to the oven. After 24 hours, the vial was removed from the oven,
and was allowed to cool to room temperature. The dioxane solvent was
removed from the reaction mixture under a stream of dry nitrogen. The
residual viscous DMSO solution was mixed with about 15 mL of water,
resulting in a 2-phase liquid mixture: an upper, clear dark amber aqueous
mixture; and a lower, viscous yellow-brown oil phase. The aqueous layer
was decanted from the oil, and the oil was washed with another 15 mL
portion of water. After again decanting off the water phase, the oil was
dissolved in about 15 mL of THF. This solution was dried over anhydrous
magnesium sulfate, and the solvent was removed under a stream of dry
nitrogen. The residual oil was dried in a vacuum oven at 65.degree. C.
for about 2 hours to give 0.696 grams of product as a red viscous oil.

Example 3

Antioxidant Potential

[0052] Antioxidant potential is evaluated using the Oxygen Radical
Absorbance Capacity (ORAC) protocol. ORAC is a chemical in-vitro method
based on the hydrogen atom transfer (HAT) mechanism (see N. Re et al.,
Free Radical Biology & Medicine, 26 (9/10), 1231 (1997)). ORAC measures
antioxidant inhibition of peroxyl radical induced oxidations and thus
reflects classical radical chain breaking antioxidant activity by H atom
transfer. In this assay, the peroxyl radical reacts with a fluorescent
probe to form a non-fluorescent product. This is quantitated using a
fluorescence measurement. Antioxidant capacity is determined by decreased
rate and amount of product formed over time. This assay depends upon the
free radical damage to the fluorescent probe resulting in the change in
its fluorescence intensity. The change of fluorescence intensity is an
indicator of the degree of free radical damage. In the presence of an
antioxidant, the inhibition of free radical damage is reflected in higher
fluorescence intensity and can be measured as antioxidant capacity
against the free radicals. The uniqueness of ORAC assay is that the
reaction is driven to completion. This allows calculation of the area
under the curve (AUC) and gives an absolute quantitation of antioxidancy
as opposed to relative measurements in many other assays.

[0053] As noted, the longer it takes to observe a decrease in
fluorescence, the higher the antioxidant (AO) potential. From the AUC for
a given antioxidant, the AUC for blank is subtracted to give its ORAC
value. The concentration of AO needed to give the same AUC values as
Trolox is calculated and used to represent the Trolox equivalent AO
Capacity (TEAC). Trolox is
((.+-.)-6-Hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid, CAS
#53188-07-1), and is used as an internal control.

[0054] The ORAC test is conducted in the stilbene-pendant nitrone
compounds of Table 1 above (inventive compounds) as well as to Vitamin C,
Vitamin E, and the following comparative compounds:

##STR00022##

Butylated hydroxytoluene (BHT)

##STR00023##

(Z)-N-pentylidenepropan-2-amine oxide (VAL-IPHA)

##STR00024##

2-Phenyl-N-tert-butylnitrone (PBN)

[0055] The inventive stilbene-pendant nitrones in the ORAC test solutions
were at a concentration of 100 micromolar, while the concentrations of
Trolox, Vitamin C, Vitamin E, BHT, PBN+BHT, and VAL-IPHA were at 100
micromolar. The TEAC values calculated from the ORAC values are listed
the Table 2.

[0056] Surprisingly, it is found that the polymeric nitrones of the
invention displayed significantly higher ORAC values compared to the
known antioxidants Vitamin E or C. It is also evident that the TEAC
values of phenolic AOs such as BHT, a non-aromatic nitrone such as
VAL-IPHA, or an aromatic nitrone such as PBN are not very high compared
to the TEAC values of the polymeric nitrones invention. The TEAC value
for a physical blend of an aromatic nitrone and a phenolic AO (PBN+BHT)
is relatively small also.